Our Department's Program has been concerned primarily with the cardiovascular-renal diseases and transplantation and is now to concentrate more on ischemic disease of the myocardium and on acute pulmonary injury. Specific studies will focus on 1) the understanding and prevention of transplant rejection and recurrent glomerulonephritis by continuing to survey the lesion in man and to establish models of the human lesion in the experimental animal; 2) the definition of the chemical basis of ultrastructural changes in disease, particularly as it affects cellular membrane systems in the lung, kidney, myocardium and vessels; 3) the determination of the effects of growth regulators and cytotoxins elaborated by lymphocytes (lymphokines, e.g., lymphotoxin) in cell culture systems on target cells and their chemical nature; 4) histocompatibility typing and cell interaction in quantitative mixed lymphocyte cultures in relationship to genetic matching in clinical transplantation; and 5) to continue to characterize and quantify the cardiac, pulmonary, vascular and renal diseases in man, with particular emphasis on the pathogenesis of acute pulmonary injury and the modulation of ischemic myocardial damage. Current approaches recognize the need for the definition of cellular injury by integrated structural, functional and compositional studies, particularly as it is reflected in the membrane systems of the cell. We are evaluating and also developing chemical methods for the detection of free radical injury in membrane phospholipids as well as immunoelectron microscopic techniques for the definitive localization of protein macromolecules in tissues and on cell membranes in model systems which are concerned with lesions in man.